id: Q9H444 gene_symbol: CHMP4B product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: CHMP4B encodes hSnf7-2, a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4B-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and endolysosomal degradation. CHMP4B is also an important paralog for human neuronal cargo turnover/autophagosome accumulation, cytokinetic abscission, viral budding, nuclear envelope sealing, plasma membrane repair, and lens transparency, but these contexts should be interpreted through the core ESCRT-III membrane-remodeling mechanism. existing_annotations: - term: id: GO:0005635 label: nuclear envelope evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0000815 label: ESCRT III complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0009898 label: cytoplasmic side of plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0032511 label: late endosome to vacuole transport via multivesicular body sorting pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0000776 label: kinetochore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0001778 label: plasma membrane repair evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Supported non-core CHMP4B plasma-membrane repair context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid topologically related ESCRT output, but it is secondary to the core MVB/endosomal ESCRT-III function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - term: id: GO:0005635 label: nuclear envelope evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0005765 label: lysosomal membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: lysosomal membrane.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0007034 label: vacuolar transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: vacuolar transport.' action: MODIFY reason: Multivesicular body sorting is the informative ESCRT-III process; vacuolar transport is too broad for human CHMP4B. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0031902 label: late endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0036258 label: multivesicular body assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: protein homodimerization activity.' action: MODIFY reason: Homodimerization is less informative than CHMP4B/Snf7-family polymerization and membrane bending. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0061952 label: midbody abscission evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody abscission.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0097352 label: autophagosome maturation evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome maturation.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to lysosome transport.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:1904930 label: amphisome membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: amphisome membrane.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16730941 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16856878 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17174262 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17500595 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17711858 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18434552 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18511562 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19523902 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21889351 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22484091 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23051622 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26496610 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:16730941 qualifier: enables review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.' action: MODIFY reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:19523902 qualifier: enables review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.' action: MODIFY reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome membrane.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0000815 label: ESCRT III complex evidence_type: NAS original_reference_id: PMID:36107470 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0001778 label: plasma membrane repair evidence_type: IDA original_reference_id: PMID:24482116 qualifier: involved_in review: summary: Supported non-core CHMP4B plasma-membrane repair context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid topologically related ESCRT output, but it is secondary to the core MVB/endosomal ESCRT-III function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:26040713 qualifier: part_of review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0005765 label: lysosomal membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: lysosomal membrane.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: plasma membrane.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: nucleus organization.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040713 qualifier: involved_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IDA original_reference_id: PMID:16554368 qualifier: located_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0051469 label: vesicle fusion with vacuole evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: vesicle fusion with vacuole.' action: MODIFY reason: The evidence supports ESCRT/MVB delivery toward lysosomes rather than CHMP4B acting as a vacuole-fusion SNARE. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061763 label: multivesicular body-lysosome fusion evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: multivesicular body-lysosome fusion.' action: MODIFY reason: The evidence supports late endosome-to-lysosome/endolysosomal transport rather than CHMP4B as a direct MVB-lysosome fusion factor. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody abscission.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:16554368 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:19234443 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane fission.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0097352 label: autophagosome maturation evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome maturation.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to lysosome transport.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:1904930 label: amphisome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: amphisome membrane.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0030496 label: midbody evidence_type: EXP original_reference_id: PMID:22422861 qualifier: located_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0031902 label: late endosome membrane evidence_type: EXP original_reference_id: PMID:15511219 qualifier: located_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33349255 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0050877 label: nervous system process evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: Supported but broad non-core CHMP4B neuronal context. action: KEEP_AS_NON_CORE reason: hSnf7-2/CHMP4B is required for human neuronal survival and cargo turnover, but nervous system process is broad compared with the underlying ESCRT/MVB cargo-sorting mechanism. supported_by: - reference_id: PMID:21975012 supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons - reference_id: PMID:21975012 supporting_text: hSnf7-1- or hSnf7-2-contaning ESCRT-III regulates the trafficking of different transmembrane cargos - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34818527 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22162750 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IMP original_reference_id: PMID:14505570 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:18209100 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:18209100 qualifier: enables review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.' action: MODIFY reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0051258 label: protein polymerization evidence_type: IDA original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0045296 label: cadherin binding evidence_type: HDA original_reference_id: PMID:25468996 qualifier: enables review: summary: 'Broad high-throughput/proximity annotation is not a core CHMP4B function: cadherin binding.' action: MARK_AS_OVER_ANNOTATED reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function. supported_by: - reference_id: PMID:25468996 supporting_text: proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: The E-cadherin proximity proteomics evidence is broad high-throughput context, not a core CHMP4B molecular function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18641129 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: macroautophagy.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0031982 label: vesicle evidence_type: IDA original_reference_id: PMID:25468996 qualifier: located_in review: summary: 'Broad high-throughput/proximity annotation is not a core CHMP4B function: vesicle.' action: MARK_AS_OVER_ANNOTATED reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function. supported_by: - reference_id: PMID:25468996 supporting_text: proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: The E-cadherin proximity proteomics evidence is broad high-throughput context, not a core CHMP4B molecular function. - term: id: GO:0000281 label: mitotic cytokinesis evidence_type: IMP original_reference_id: PMID:21310966 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: mitotic cytokinesis.' action: MODIFY reason: CHMP4B is specifically implicated in ESCRT-dependent midbody abscission rather than all of mitotic cytokinesis. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis proposed_replacement_terms: - id: GO:0061952 label: midbody abscission - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:21310966 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:26040712 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005635 label: nuclear envelope evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0010458 label: exit from mitosis evidence_type: IMP original_reference_id: PMID:26040712 qualifier: involved_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: exit from mitosis.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:21310966 qualifier: located_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040712 qualifier: involved_in review: summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling. supported_by: - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: GFP-CHMP4B transiently localises to telophase nuclei - term: id: GO:0090148 label: membrane fission evidence_type: IMP original_reference_id: PMID:21310966 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane fission.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:24095276 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0000815 label: ESCRT III complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0036258 label: multivesicular body assembly evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0006914 label: autophagy evidence_type: TAS original_reference_id: PMID:21118109 qualifier: involved_in review: summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.' action: ACCEPT reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0030117 label: membrane coat evidence_type: IDA original_reference_id: PMID:24878737 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane coat.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:17701905 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytoplasm.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005768 label: endosome evidence_type: IDA original_reference_id: PMID:17701905 qualifier: located_in review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: endosome.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0036438 label: maintenance of lens transparency evidence_type: IMP original_reference_id: PMID:17701905 qualifier: involved_in review: summary: Supported non-core CHMP4B lens-transparency disease/physiology context. action: KEEP_AS_NON_CORE reason: CHMP4B variants cause dominant cataracts and support a lens-transparency phenotype, but this phenotype does not redefine the core ESCRT-III molecular function. supported_by: - reference_id: PMID:17701905 supporting_text: plays a vital role in the maintenance of lens transparency - reference_id: PMID:17701905 supporting_text: key component of the endosome sorting complex required - term: id: GO:0046755 label: viral budding evidence_type: IMP original_reference_id: PMID:17701905 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: viral budding.' action: MODIFY reason: The viral-budding evidence is specifically host ESCRT-mediated budding, not generic viral budding. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission proposed_replacement_terms: - id: GO:0039702 label: viral budding via host ESCRT complex - term: id: GO:0010824 label: regulation of centrosome duplication evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of centrosome duplication.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: UniProt:Q9H444 supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase - term: id: GO:0090611 label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:22547407 qualifier: involved_in review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway.' action: MODIFY reason: This obsolete ubiquitin-independent catabolic process term should be replaced by the non-obsolete MVB sorting pathway term. supported_by: - reference_id: PMID:22547407 supporting_text: PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IGI original_reference_id: PMID:24107264 qualifier: involved_in review: summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: PMID:24878737 supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: Plausible but broad non-core CHMP4B extracellular-exosome context. action: KEEP_AS_NON_CORE reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan - reference_id: PMID:18209100 supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: protein homodimerization activity.' action: MODIFY reason: Homodimerization is less informative than CHMP4B/Snf7-family polymerization and membrane bending. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:21975012 qualifier: part_of review: summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21975012 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:21975012 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: nucleus.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:21975012 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytoplasm.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0006620 label: post-translational protein targeting to endoplasmic reticulum membrane evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: 'Unsupported CHMP4B annotation: post-translational protein targeting to ER membrane.' action: REMOVE reason: PMID:21975012 supports hSnf7-2/CHMP4B in neuronal endosomal cargo turnover and autophagosome accumulation, but does not support a role in post-translational targeting to the ER membrane. supported_by: - reference_id: PMID:21975012 supporting_text: hSnf7-2-containing ESCRT-III differentially regulates the turnover of distinct transmembrane cargos in human neurons - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: PMID:21975012 supports neuronal cargo turnover and autophagosome accumulation, not post-translational targeting to the ER membrane. - term: id: GO:0009898 label: cytoplasmic side of plasma membrane evidence_type: IDA original_reference_id: PMID:18209100 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: Plausible but broad non-core CHMP4B extracellular-exosome context. action: KEEP_AS_NON_CORE reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan - reference_id: PMID:18209100 supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12860994 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:20458337 qualifier: located_in review: summary: Plausible but broad non-core CHMP4B extracellular-exosome context. action: KEEP_AS_NON_CORE reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function. supported_by: - reference_id: UniProt:Q9H444 supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan - reference_id: PMID:18209100 supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21543490 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917693 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917700 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668389 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668395 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668398 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668405 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668415 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668419 qualifier: located_in review: summary: 'True or plausible broad CHMP4B location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Cytoplasm. Cytosol. Late endosome membrane - reference_id: UniProt:Q9H444 supporting_text: Membrane-associated - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:22724069 qualifier: located_in review: summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.' action: KEEP_AS_NON_CORE reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here. supported_by: - reference_id: PMID:22422861 supporting_text: CHMP4B was again the sole paralog required - reference_id: PMID:22422861 supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately - reference_id: PMID:21310966 supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments - reference_id: UniProt:Q9H444 supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20208530 qualifier: enables review: summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes. supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: file:human/CHMP4B/CHMP4B-notes.md supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function. - term: id: GO:0180020 label: membrane bending activity evidence_type: IDA original_reference_id: PMID:18209100 qualifier: enables review: summary: New CHMP4B molecular-function annotation supported by direct hSnf7-2 filament/membrane curvature evidence. action: NEW reason: PMID:18209100 directly includes hSnf7-2/CHMP4B and shows that CHMP4-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic binding terms. supported_by: - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:12860994 title: The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. findings: - statement: CHMP4B/CHMP4b associates with ALIX and is implicated in MVB sorting and endosomal localization. - id: PMID:14505570 title: The protein network of HIV budding. findings: [] - id: PMID:14519844 title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. findings: [] - id: PMID:15511219 title: Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting. findings: - statement: CHMP6 interacts directly with CHMP4B/Shax and regulates endosomal cargo sorting. - id: PMID:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. findings: [] - id: PMID:16505166 title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. findings: [] - id: PMID:16554368 title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. findings: [] - id: PMID:16730941 title: 'A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.' findings: [] - id: PMID:16856878 title: CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and functions in the endosomal sorting pathway. findings: [] - id: PMID:17174262 title: HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. findings: [] - id: PMID:17500595 title: Huntingtin interacting proteins are genetic modifiers of neurodegeneration. findings: [] - id: PMID:17701905 title: CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q. findings: - statement: CHMP4B mutations cause autosomal dominant cataracts and support a lens-transparency phenotype. - id: PMID:17711858 title: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. findings: [] - id: PMID:17984323 title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. findings: [] - id: PMID:18209100 title: Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. findings: - statement: Direct hSnf7-2/CHMP4B evidence supports ESCRT-III filament polymerization, membrane bending, and negative-curvature budding. - id: PMID:18434552 title: The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. findings: [] - id: PMID:18511562 title: ALIX-CHMP4 interactions in the human ESCRT pathway. findings: [] - id: PMID:18641129 title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19234443 title: Membrane scission by the ESCRT-III complex. findings: [] - id: PMID:19523902 title: A crescent-shaped ALIX dimer targets ESCRT-III CHMP4 filaments. findings: [] - id: PMID:20208530 title: PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. findings: [] - id: PMID:20458337 title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. findings: [] - id: PMID:20588296 title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.' findings: [] - id: PMID:20616062 title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. findings: [] - id: PMID:21118109 title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. findings: [] - id: PMID:21310966 title: Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. findings: - statement: ESCRT-III-dependent filaments localize to constriction zones and support cortical constriction during abscission. - id: PMID:21543490 title: Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15. findings: [] - id: PMID:21889351 title: The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release. findings: [] - id: PMID:21975012 title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons. findings: - statement: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation and altered transmembrane cargo turnover. - id: PMID:22162750 title: Structure of the Bro1 domain protein BROX and functional analyses of the ALIX Bro1 domain in HIV-1 budding. findings: [] - id: PMID:22422861 title: ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. findings: - statement: CHMP4B is the CHMP4 paralog required for MHC-I degradation, HIV release, and completion of cytokinesis in this study. - id: PMID:22484091 title: Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B. findings: [] - id: PMID:22547407 title: ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. findings: - statement: ALIX-CHMP4/ESCRT-III mediates ubiquitin-independent PAR1 sorting to MVB/lysosomal degradation. - id: PMID:22724069 title: The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis. findings: [] - id: PMID:23051622 title: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:24095276 title: Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation. findings: [] - id: PMID:24107264 title: ESCRT requirements for EIAV budding. findings: [] - id: PMID:24482116 title: ESCRT machinery is required for plasma membrane repair. findings: [] - id: PMID:24878737 title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding. findings: [] - id: PMID:25468996 title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics. findings: - statement: E-cadherin BioID/proteomics provides broad proximity evidence that should not be treated as core CHMP4B molecular function. - id: PMID:26040712 title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. findings: [] - id: PMID:26040713 title: ESCRT-III controls nuclear envelope reformation. findings: [] - id: PMID:26496610 title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33349255 title: Lethal (2) giant discs (Lgd)/CC2D1 is required for the full activity of the ESCRT machinery. findings: [] - id: PMID:34818527 title: The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:36107470 title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission. findings: [] - id: Reactome:R-HSA-3159232 title: Recruitment Of HIV Virion Budding Machinery findings: [] - id: Reactome:R-HSA-917693 title: ESCRT Disassembly findings: [] - id: Reactome:R-HSA-917700 title: MVB Vesicle Formation findings: [] - id: Reactome:R-HSA-9668389 title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations findings: [] - id: Reactome:R-HSA-9668395 title: CHMP7 binds CC2D1B findings: [] - id: Reactome:R-HSA-9668398 title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex findings: [] - id: Reactome:R-HSA-9668405 title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin findings: [] - id: Reactome:R-HSA-9668415 title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope findings: [] - id: Reactome:R-HSA-9668419 title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites findings: [] - id: file:human/CHMP4B/CHMP4B-notes.md title: Local curation notes for CHMP4B findings: - statement: Local synthesis identifies CHMP4B/Snf7-2 ESCRT-III polymerization, membrane bending, and MVB/endolysosomal sorting as core functions, with autophagy and other ESCRT outputs retained in context. - id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md title: Falcon deep research report for CHMP4B findings: - statement: Falcon synthesis agrees with cached primary evidence that CHMP4B is a non-enzymatic ESCRT-III membrane-remodeling scaffold involved in reverse-topology constriction and scission. core_functions: - molecular_function: id: GO:0180020 label: membrane bending activity description: CHMP4B/Snf7-2 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0090148 label: membrane fission locations: - id: GO:0031902 label: late endosome membrane - id: GO:0032585 label: multivesicular body membrane supported_by: - reference_id: UniProt:Q9H444 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - description: CHMP4B-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and endosomal cargo sorting toward lysosomal degradation, including ubiquitin-dependent cargo and ALIX/CHMP4-dependent ubiquitin-independent cargo routes. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway locations: - id: GO:0032585 label: multivesicular body membrane - id: GO:0005768 label: endosome supported_by: - reference_id: UniProt:Q9H444 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9H444 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:12860994 supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:22547407 supporting_text: PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** - description: CHMP4B/Snf7-2 contributes to proteostasis through ESCRT-dependent endolysosomal cargo turnover and autophagy/autophagosome maturation contexts; direct human-neuron knockdown causes autophagosome accumulation and altered transmembrane cargo turnover. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0097352 label: autophagosome maturation - id: GO:0016236 label: macroautophagy - id: GO:1902774 label: late endosome to lysosome transport locations: - id: GO:0000421 label: autophagosome membrane - id: GO:1904930 label: amphisome membrane - id: GO:0005765 label: lysosomal membrane supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation - reference_id: PMID:21975012 supporting_text: reduced expression of hSnf7-1 or hSnf7-2 led to accumulation of epidermal growth factor receptor - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:24095276 supporting_text: STX13 is a genetic modifier of ESCRT-III dysfunction and participates in the maturation of phagophores into closed autophagosomes - reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission** proposed_new_terms: [] suggested_questions: - question: Which CHMP4 paralog is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation in endogenous cells? - question: Should GO annotations distinguish CHMP4B direct membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, nuclear envelope sealing, and cytokinetic abscission? - question: How do CHMP4B-CHMP2B-enriched ESCRT-III assemblies differ from CHMP4A-CHMP2A assemblies in neuronal endosomal cargo turnover and proteostasis? suggested_experiments: - description: Use endogenous CHMP4B tagging plus acute depletion/rescue during starvation-induced autophagy and selective cargo turnover assays to image recruitment to phagophores, autophagosomes, amphisomes, and endosomes. hypothesis: If CHMP4B directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region. - description: Compare wild-type CHMP4B with ALIX-binding, CHMP2B-interaction, and C-terminal autoinhibition mutants in MVB cargo sorting, HIV budding, cytokinetic abscission, and neuronal receptor turnover assays. hypothesis: CHMP4B uses the same Snf7-family filament core across ESCRT outputs, but partner and recruitment requirements differ by membrane context. - description: Biochemically reconstitute CHMP4B-containing human ESCRT-III polymers with CHMP2B, CHMP3, CHMP6, and VPS4 and test membrane bending/scission on defined liposomes. hypothesis: CHMP4B contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.